Reproductive Endocrinology Reference Intervals for Transgender Women on Stable Hormone Therapy.

Anti-Müllerian Hormone in Girls with Premature Adrenarche: The Impact of Polycystic Ovary Syndrome History in their Mothers

Introduction: Poor ovarian responders are the most challenging patients in reproductive medicine and no successful treatment has been proposed. Androgens are thought to play an important role during early folliculogenesis and diminished levels are associated with decreased ovarian sensitivity to follicle-stimulating hormone. This study aimed to determine whether pretreatment with testosterone improves the results in poor responders undergoing in vitro fertilisation (IVF). Materials and methods: This observational pilot study enrolled 33 poor responders undergoing IVF. Eleven patients were pretreated with 250 mg intramuscular testosterone and compared to a control group of 22 patients. The participants were tested for free testosterone, dehydroepiandrosterone sulfate, sex hormone binding globulin, and anti-mullerian hormone (AMH). Results: The two groups had similar baseline characteristics. Significant improvement was reached in the hormones free testosterone, dehydroepiandrosterone sulfate, and sex hormone binding globulin in the testosterone-pretreatment group. No difference was detected in antral follicle count (5.06 versus 4.24); AMH (0.51 versus 0.53), mature oocytes (2.2 versus 2.32), and the number of embryos (1.2 versus 1.33) between the study and control groups, respectively. There was a slow improvement in fertilisation rate but without any significance (62.97% versus 57.61%). However, the cancellation rate of the ovarian stimulation was much greater in the control group (18.18%) in comparison with the study group (0.0%). Pregnancy rate (PR) in the testosterone group was higher than controls (PR per cycle: 27.3% versus 4.6; p=0.09). Conclusion: Based on the limited number of patients studied, pretreatment with testosterone seems to improve PR and cancellation rate in poor responders but failed to affect antral follicle count, AMH, and the number of mature oocytes and embryos. Given these results, further research would provide more certainty.

Differential effects of oestrogen on class-switch recombination of B cells dependent on sex chromosome complement: a cross-sectional study

Differential effects on the androgen status of postmenopausal women treated with tibolone and continuous combined estradiol and norethindrone acetate replacement therapy

An unknown proportion of transsexual women (defined as post-operative male-to-female transsexuals on oestrogen replacement) experience hypoactive sexual desire disorder (HSDD). It has been suggested that the absence of ovarian androgen production together with oestrogen treatment-related increase in sex hormone-binding globulin (SHBG) levels could be leading to HSDD, due to low levels of biologically available testosterone. This study wishes to document the HSDD prevalence among transsexual women and the possible association to androgen levels. Cross-sectional study. Transsexual women (n=62) and a control group of ovulating women (n=30) participated in this study. Questionnaires measuring sexual desire (sexual desire inventory) and relationship and sexual satisfaction (Maudsley Marital Questionnaire) were completed. Serum levels of total testosterone, LH and SHBG were measured in blood samples obtained at random in transsexual women and in the early follicular phase in ovulating women. The transsexual group had lower levels of total and calculated free testosterone (both P<0.001) than the ovulating women. HSDD was reported in 34% of the transsexual and 23% of the ovulating women (P=0.30). Both groups reported similar levels of sexual desire (P=0.97). For transsexual women, no significant correlation was found between sexual desire and total (P=0.64) or free testosterone (P=0.82). In ovulating women, these correlations were significant (P=0.006, resp. P=0.003). HSDD is reported in one-third of transsexual women. This prevalence is not substantially different from controls, despite markedly lower (free) testosterone levels, which argues against a major role of testosterone in this specific group.

Eye gaze patterns of cisgender men and women were observed while they viewed photographs of transgender and cisgender women. Past scene perception research suggested that body regions that are consistent or inconsistent with one’s expectations for transgender women’s bodies could attract eye gaze while viewing a transgender woman. We did observe a tendency for participants to view body regions that were consistent with their expectations for transgender women’s bodies more than inconsistent body regions. Evolutionary psychological research suggested eye gaze should be drawn to chests. If a woman’s chest area is important to assess for mate selection related reasons, participants should have viewed the chest more than other regions and male participants should view the chest more than female participants. We found mixed support for evolutionary theory. In some analyses it appeared the chest did attract eye gaze more than other less evolutionarily important body regions while in others it did not. Contradicting evolutionary psychological theory, we did not observe a tendency for male viewers to look more than female viewers at a transgender or cisgender woman’s chest.

Objectives: The purpose of this study was to determine the age-specific reference ranges for some important male sex steroid hormones, prostate-specific antigen (PSA), insulin-like growth factor-1 (IGF-1), and IGF binding protein-3 (IGFBP-3), for the Kuwaiti population. Subjects and Methods: Blood samples were taken from 398 consenting, fasting, healthy Kuwaiti males aged 15–80 years between 8.00 a.m. and 12.00 noon. The serum concentrations of total testosterone (TT), dehydro-epiandrosterone sulfate (DHEAS), androstenedione (ADT), sex hormone binding globulin, luteinizing hormone (LH), follicle-stimulating hormone (FSH), prolactin, PSA, IGF-1 and IGFBP-3 were determined. A distribution curve was plotted and age-specific reference levels were determined for each analyte. The reference interval for parameters with a normal distribution (Gaussian) was mean ± 2 SD, while for the non-normal distribution (non-Gaussian), it was 2.5–97.5 percentile. The reference intervals for the analytes obtained from this study were compared with those suggested by the kit manufacturers and currently used by the Ministry of Health, Kuwait Laboratories (MOHKL). Results: Serum IGFBP-3 and ADT had normal distribution while other analytes had non-normal distribution. The reference intervals from this study, manufacturers kit and MOHKL were as follows: TT 3–31, 9–60, 8–35 nmol/l; DHEAS 0.9–11, 1.0–7.3, 2.2– 15.2 µmol/l; ADT 0.5–4.3, 0.8–2.8, 2.0–9.2 nmol/l; LH 1–11, 0.8–7.6, 0.4–5.7 mIU/l; FSH 0.5–11, 0.7–11.1, 1.1–13.5 mIU/l; prolactin 42–397, 53–360, 80–230 nmol/l; IGF-1 41–542, 78–956, 71–261 ng/ml; IGFBP-3 88– 2,090, 900–4,000, 900–4,000 ng/ml, and PSA 0–3.1, 0–4, 0–4 ng/ml, respectively. Conclusion: These data indicate that for Kuwaitis lower reference ranges must be used for serum TT, DHEAS, ADT, IGFBP-3 and PSA. There is no need to change the currently used reference interval for FSH whereas higher values must be used for LH, prolactin, and IGF-1.

To compare ethnic differences in total, free and bioavailable testosterone amongst young healthy South Asian and Caucasian men. Cross-sectional study of 134 healthy men (age 20-40 years) of South Asian (n = 67) or Caucasian (n = 67) origin, recruited from hospital staff and students working in Newport, UK. Subjects were excluded if they had a fasting plasma glucose >5.9 mmol/l, central obesity [waist circumference ≥ 94 cm (Caucasian) or ≥ 90 cm (South Asian)] or significant other disease. Fasting plasma glucose, total testosterone (determined by immunoassay and mass spectrometry), albumin, sex hormone-binding globulin (SHBG) and insulin were measured. Free and bioavailable testosterone were calculated using Vermeulen's formula, and insulin resistance was estimated by HOMA-IR. The South Asians were slightly older (P = 0.04), shorter (P < 0.001), lighter (P < 0.001), more insulin resistant (P = 0.006), and had a lower body mass index BMI (P = 0.012), waist circumference (P = 0.043) and SHBG (P = 0.001) than the Caucasians. Total testosterone was significantly lower in South Asians (mass spectrometry: geometric mean 16.3 nmol/l; 95% reference interval 9.3-28.6 nmol/l) compared with Caucasians (mass spectrometry: geometric mean 18.4 nmol/l; 95% reference interval 10.6-31.9 nmol/l; P = 0.015), but calculated free and bioavailable testosterone were not different between groups. Adjusting for HOMA-IR, but not BMI or waist circumference, partly attenuated the differences in total testosterone. Total, but not free, testosterone concentrations are lower in healthy South Asian men than in Caucasians. These differences are apparent at a young age and may be partly attributable to alterations in insulin sensitivity.

ObjectiveThe inclusion of transgender athletes in competitive sports has promoted significant dialogue and controversy among exercise-related professionals. The objective of this study was to investigate body composition, exercise-related performance parameters...

Background: PCOS affects 5-15% of females of reproductive age and frequently manifests in adolescence. One of its diagnostic criteria is presence of polycystic ovary morphology (PCOM); however, this criterion is based on adult data obtained by transvaginal ultrasound thus may not be relevant to younger patients. AMH represents an alternative marker for PCOM as it is produced by preantral ovarian granulosa cells, which are increased in this condition. This study uses MRI, a noninvasive and accurate method, to determine FC and OV in young patients with PCOS and controls. Aims: 1. To determine if AMH is different in PCOS compared to controls; 2. To examine the relationship between AMH and FC and OV by MRI in PCOS and controls; 3. To determine the relationship between AMH and androgens and insulin resistance in PCOS and controls. Methods: Healthy nonobese adolescents and young adults with PCOS (n=12) and controls (n=12), (mean age 19.7 ± 3.2 years, BMI 23.1 ± 3.2 kg/m2) participated. Labs after an overnight fast included AMH, LH, FSH, estradiol, total and free testosterone, androstenedione, DHEAS, and a 2h OGTT with glucose and insulin levels. HOMA-IR and insulin area under the curve (iAUC) were calculated. Whole body dual-energy x-ray absorptiometry (DXA) scan for percentage body fat (%BF) and ovarian MRI for OV and FC were obtained. Results: Compared to controls, PCOS had higher AMH (10.7 ± 5.8 vs 5.0 ± 2.5 ng/mL. Reference range: 1.05-12.86 ng/mL), total and free testosterone, androstenedione and DHEAS (P<0.003 for all). HOMA-IR, iAUC , BMI and %BF were similar between the groups. AMH correlated with total testosterone (r=0.66, p<0.03) and to FC (r=0.88, p=0.0002), but not with free testosterone, androstenedione, DHEA-S, LH, HOMA-IR, iAUC or OV by MRI. Conclusions: In this small study of young and nonobese patients, AMH was higher in PCOS than controls and highly correlated with FC using ovarian MRI and to testosterone levels. These findings support the use of AMH as a minimally invasively additional marker to assist in the diagnosis of PCOS.

Anti-Müllerian hormone (AMH) is produced by granulosa cells surrounding follicles that have undergone recruitment from the primordial follicle pool but have not been selected for dominance (preantral and early antral follicles). In healthy girls, serum levels of AMH vary considerably between individuals. We aimed to evaluate the AMH level in girls with premature thelarche (PT) and central precocious puberty (CPP). Girls with CPP (n=21), PT (n=24) and a control prepubertal group (n=22) were included in the study. AMH levels were significantly higher in the PT group than the prepubertal control group and similar to the CPP group. AMH levels in the CPP group were similar to the prepubertal control group. AMH levels showed a significant negative correlation with luteinizing hormone (LH), free testosterone and dehydroepiandrosterone sulphate (DHEAS) levels in the PT group. AMH levels were negatively correlated with height standard deviation score (HSDS), body mass index (BMI) SDS values and positively correlated with sex hormone binding globulin (SHBG) levels in the CPP group. These levels were positively correlated with SHBG levels in the control prepubertal group. Serum AMH levels in girls with PT was found to be higher than in prepubertal girls. AMH levels in the CPP group were not different compared with the PT and control groups.

BackgroundFindings from observational studies suggest that sex hormone-binding globulin (SHBG) and endogenous sex hormones may be mediators of the putative relation between coffee consumption and lower risk of type 2 diabetes. The objective of this study was to evaluate the effects of caffeinated and decaffeinated coffee on SHBG and sex hormone levels.FindingsAfter a two-week run-in phase with caffeine abstention, we conducted an 8-week parallel-arm randomized controlled trial. Healthy adults (n = 42) were recruited from the Boston community who were regular coffee consumers, nonsmokers, and overweight. Participants were randomized to five 6-ounce cups of caffeinated or decaffeinated instant coffee or water (control group) per day consumed with each meal, mid-morning, and mid-afternoon. The main outcome measures were SHBG and sex hormones [i.e., testosterone, estradiol, dehydroepiandrosterone sulfate].No significant differences were found between treatment groups for any of the studied outcomes at week 8. At 4 weeks, decaffeinated coffee was associated with a borderline significant increase in SHBG in women, but not in men. At week 4, we also observed several differences in hormone concentrations between the treatment groups. Among men, consumption of caffeinated coffee increased total testosterone and decreased total and free estradiol. Among women, decaffeinated coffee decreased total and free testosterone and caffeinated coffee decreased total testosterone.ConclusionsOur data do not indicate a consistent effect of caffeinated coffee consumption on SHBG in men or women, however results should be interpreted with caution given the small sample size. This is the first randomized trial investigating the effects of caffeinated and decaffeinated coffee on SHBG and sex hormones and our findings necessitate further examination in a larger intervention trial.

Testosterone (T), sex hormone binding globulin (SHBG), free testosterone (FT) and bioavailable testosterone (BAT) are commonly employed tests in pediatric endocrinology and all require age-dependent reference intervals for interpretation. The common methods used to derive these reference intervals require decisions about data shape and/or age partition thresholds, which can result in sharp differences between age groups, particularly for pubescent children. Partitioning also results in a form of data loss, where data from one age-bin is completed disconnected from the adjacent age-bins. Non-parametric continuous reference intervals methods have previously been developed to avoid some of these drawbacks. These strategies use all the available data and smooth transitions between ages avoiding partitioning. However, the fitting process involves selection and adjustment of many parameters and it can be difficult to maintain a reproducible approach. Here we provide a workflow for non-parametric continuous reference intervals applied to T, FT, BAT, and SHBG using the R language quantregGrowth package. T measurements were determined by LC-MS/MS, FT and BAT were calculated, and SHBG was measured on the Roche Cobas e601. The continuous interval methodology is described in detail with code examples and illustrations for reproducibility.

Dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS) age-related withdrawal is very likely to be involved in the aging process and the onset of age-related diseases, giving rise to the question of whether preventing or compensating the decline of these steroids may have endocrine and clinical benefits. The aim of the present trial was to evaluate the endocrine, neuroendocrine and clinical consequences of a long-term (1 year), low-dose (25 mg/day) replacement therapy in a group of aging men who presented the clinical characteristics of partial androgen deficiency (PADAM). Circulating DHEA, DHEAS, androstenedione, total testosterone and free testosterone, dihydrotestosterone (DHT), progesterone, 17-hydroxyprogesterone, allopregnanolone, estrone, estradiol, sex hormone binding globulin (SHBG), cortisol, follicle stimulating hormone (FSH), luteinizing hormone (LH), growth hormone (GH) and insulin-like growth factor 1 (IGF-1) levels were evaluated monthly to assess the endocrine effects of the therapy, while β-endorphin values were used as a marker of the neuroendocrine effects. A Kupperman questionnaire was performed to evaluate the subjective symptoms before and after treatment.The results showed a great modification of the endocrine profile; with the exception of cortisol levels, which remained unchanged, DHEA, DHEAS, androstenedione, total and free testosterone, DHT, progesterone, 17-hydroxyprogesterone, estrone, estradiol, GH, IGF-1 and β-endorphin levels increased significantly with respect to baseline values, while FSH, LH and SHBG levels showed a significant decrease. The Kupperman score indicated a progressive improvement in mood, fatigue and joint pain.In conclusion, the present study demonstrates that 25 mg/day of DHEA is able to cause significant changes in the hormonal profile and clinical symptoms and can counteract the age-related decline of endocrine and neuroendocrine functions. Restoring DHEA levels to young adult values seems to benefit the age-related decline in physiological functions but, however promising, placebo-controlled trials are required to confirm these preliminary results.

Does in utero exposure to constituents of cigarette smoke have a programming effect on daughters' age of menarche and markers of long-term reproductive health? In utero exposure to constituents of cigarette smoke was associated with earlier age of menarche and--to a lesser extent--changes in the testosterone profile of the young women. Studies observe potential effects of in utero exposure to constituents of cigarette smoke on the intrauterine formation of female gonads, but the consequences on long-term reproductive health in daughters remain unclear. A prospective cohort study was designed using data from 965 pregnant women enrolled prior to a routine 30th-week antenatal examination at a midwifery practice in Denmark from 1988 to 1989 and a follow-up of their 19-21-year-old daughters in 2008. The pregnant women provided information on lifestyle factors during pregnancy, including the exact number of cigarettes smoked per day during the first and the second trimesters. A total of 438 eligible daughters were asked to complete a web-based questionnaire on reproductive health and subsequently invited to participate in a clinical examination during 2008. Of the 367 daughters (84%) who answered the questionnaire, 267 (61%) agreed to further examination. Information on menstrual pattern was provided at examination, blood samples were drawn to be analyzed for serum levels of reproductive hormones [FSH, LH, estradiol (E(2)), sex hormone-binding globulin, anti-Müllerian hormone, dehydroepiandrosterone-sulphate (DHEAS), free testosterone and free E(2)] and number of follicles (2-9 mm) were examined by transvaginal ultrasound. The daughters were divided into three exposure groups according to the level of maternal smoking during first trimester [non-exposed (reference), low-exposed (mother smoking >0-9 cigarettes/day) and high-exposed (mother smoking ≥ 10 cigarettes/day)]. Data were analyzed by multiple regression analyses in which we adjusted for potential confounders. Both crude and adjusted test for trend were carried out using maternal smoking during the first trimester as a continuous variable. We observed an inverse association between in utero exposure to constituents of cigarette smoke and age of menarche (P = 0.001). Daughters exposed to >0-9 cigarettes/day debuted with -2.7 [95% confidence interval (CI) -5.2 to -0.1] percentage earlier age of menarche, whereas daughters exposed to ≥ 10 cigarettes/day had -4.1 (95% CI: -6.6 to -1.5) percentage earlier age of menarche corresponding to 6.5 (95% CI: -10.7 to -2.2) months. There was a non-significant tendency towards lower levels of testosterone and DHEAS with increasing in utero exposure to constituents of cigarette smoke but no associations with follicle number, cycle length or serum levels of the other reproductive hormones were observed. We collected information on age of menarche retrospectively but the recall time was relatively short (2-10 years) and the reported values were within the normal range of Caucasians. Analyses of reproductive hormones are presented only for the group of daughters who were non-users of hormonal contraceptives because users were excluded, leaving only a low number of daughters available for the analyses (n = 75), as reflected in the wide CIs. The analyses of hormones were further adjusted for menstrual phase at time of clinical examination (follicular, ovulation and luteal phase) because blood samples were not collected on a specific day of the menstrual cycle. This study supports the limited evidence of an inverse association between maternal smoking during pregnancy and age of menarche and further addresses to what extent reproductive capacity and hormones may be programmed by maternal smoking during pregnancy. A trend toward earlier maturation of females is suggested to have implications on long-term reproductive function. Supported by a scholarship from The Lundbeck Foundation (R93-A8476). No conflict of interest declared.